Brussels, 08 Nov 2005
1. Introduction and Executive Summary
EuropaBio welcomes the initiative of the EMEA and the continuing opportunity which is given to all stakeholders to comment on the draft Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (ref. EMEA/CHMP/437/04) released for consultation in May 2005 (hereinafter "the draft Guideline"). We welcome the willingness of the EMEA to develop in a transparent manner additional, more refined and detailed regulatory guidance tools to approve products and to give companies, that wish to apply for a marketing authorisation for a similar biological medicinal product (hereinafter "a biosimilar medicine"), a clearer indication as to what the regulatory requirements are.
EuropaBio, the European Association for Bioindustries, has 55 corporate members operating worldwide and 25 national biotechnology associations representing some 1500 small and medium sized enterprises (SMEs) involved in research and development, testing, manufacturing and distribution of biotechnology products.
EuropaBio is following closely the development of the rules governing the approval of biosimilar medicines from the beginning of the review of the pharmaceutical legislation. This is an extremely important issue for all parties concerned, from patients to biosimilar and innovative industries, and healthcare authorities. It has also historically been a very complex issue from a scientific standpoint since biosimilar medicines are clearly not generic products, and experience amongst regulatory authorities with these kinds of medicines is currently limited.
Set against this background, EuropaBio believes that the introduction of biosimilar medicines should be subject to the same scientifically sound and rigorous regulatory considerations applied to the innovator product in order to ensure that patient safety continues to be protected. EuropaBio is convinced that any potential cost savings of using biosimilar medicines should not override the objective of public health protection, which remains the primary consideration in approval of biosimilar medicines. If certain fundamental principles are maintained, and innovator rights are fully respected, EuropaBio believes that through a sound public process, the EMEA can develop a considered approach to the approval of safe and effective biosimilar medicines. Despite the above, EuropaBio believes that there has been virtually no consideration of certain fundamental issues which should be addressed before moving forward with the approval of biosimilar medicines.
For this reason, EuropaBio believes that it is inappropriate to proceed with the approval of biosimilar medicines in the European Union before all unexplored and/or unanswered issues have been fully discussed and carefully considered. EuropaBio believes that a prerequisite to the final adoption of clear guidance in this field is a more comprehensive and public discussion of these issues with all relevant authorities and stakeholders, including with healthcare professionals and the patients.
The thrust of EuropaBio's comments is to request the following regulatory and legal issues to be fully addressed before moving forward with the authorisation of biosimilar medicines:
- Biosimilar medicines, or "biosimilars", are complex molecules; they are not generics and necessitate appropriate preclinical and clinical testing before being delivered to patients.
- There should be no relaxation of the approval standards for biosimilar medicines. The approval procedure for biosimilar medicines must be as scientifically rigorous as the procedure for the approval of an innovator biological medicinal product
- The choice of the reference product should be carefully assessed by the EMEA during the biosimilar approval process.
- Proposed clinical trial programmes for biosimilar medicines should not place patients at risk. The principles of Good Clinical Practices and Good Manufacturing Practices should fully apply during the conduct of biosimilar clinical trials.
- It is not advisable for patient safety reasons to extrapolate clinical data from one clinical indication to a different indication. The draft Guideline should therefore be amended in order to state clearly that extrapolation is not appropriate in most of the cases.
- The safety profile of any biosimilar medicine must be demonstrated to be similar to the reference product before approval. It is not appropriate to state in the draft Guideline that a biosimilar medicine may have a different safety profile than the reference product. The draft Guideline should therefore be amended in this respect.
- A risk management plan should be required for all biosimilar products.
- As it consistently has in the past, the EMEA must continue to ensure that confidential proprietary information of EuropaBio's members is not used, relied upon or disclosed during the guidelines drafting process or approval of biosimilars, except as provided by the law.
- The EMEA should not review or authorize any biosimilar medicine before all appropriate biosimilar guidance documents have been fully adopted. - A detailed impact assessment should be conducted.